Broad diversity of Mycobacterium tuberculosis complex strains isolated from humans and cattle in Northern Algeria suggests a zoonotic transmission cycle

Mycobacterium tuberculosis complex (MTBC) comprises closely related species responsible for human and animal tuberculosis (TB). Efficient species determination is useful for epidemiological purposes, especially for the elucidation of the zoonotic contribution. In Algeria, data on MTBC genotypes are largely unknown. In this study, we aimed to investigate the occurrence and diversity of MTBC genotypes causing human and bovine TB in Northern Algeria. During a two-year sampling period (2017–2019) in two regions of Northern Algeria, we observed an overall prevalence of 6.5% of tuberculosis (TB) among slaughtered cattle, which is higher than previous Algerian data yet comparable to neighboring countries. A total of 296 Mycobacterium tuberculosis complex (MTBC) isolates were genotyped by spoligotyping: 181 from tissues with TB-like lesions collected from 181 cattle carcasses and 115 from TB patients. In human isolates, we identified 107 M. tuberculosis, seven M. bovis and one “M. pinnipedii-like”, while for bovine samples, 174 isolates were identified as M. bovis, three as M. caprae, three as “M. pinnipedii-like” and one as “M. microti-like”. The majority of isolates (89.2%) belonged to 72 different known Shared International Types (SIT) or M. bovis spoligotypes (SB), while we also identified seven new SB profiles (SB2695 to SB2701). Twenty-eight of the SB profiles were new to Algeria. Our data suggest zoonotic transmission in Sétif, where significantly more TB was observed among cattle (20%) compared to the slaughterhouses from the three other regions (5.4%–7.3%) (p < 0.0001), with the isolation of the same M. bovis genotypes from TB patients. The present study showed a high genetic diversity of MTBC isolated from human and cattle in Northern Algeria. Even though relatively small in terms of numbers, our data suggest the zoonotic transmission of TB from cattle to humans, suggesting the need for stronger eradication strategies for bovine TB.     

A Meta-Analysis of Retinoblastoma Copy Numbers Refines the List of Possible Driver Genes Involved in Tumor Progression

BackgroundWhile RB1 loss initiates retinoblastoma development, additional somatic copy number alterations (SCNAs) can drive tumor progression. Although SCNAs have been identified with good concordance between studies at a cytoband resolution, accurate identification of single genes for all recurrent SCNAs is still challenging. This study presents a comprehensive meta-analysis of genome-wide SCNAs integrated with gene expression profiling data, narrowing down the list of plausible retinoblastoma driver genes.MethodsWe performed SCNA profiling of 45 primary retinoblastoma samples and eight retinoblastoma cell lines by high-resolution microarrays. We combined our data with genomic, clinical and histopathological data of ten published genome-wide SCNA studies, which strongly enhanced the power of our analyses (N = 310).ResultsComprehensive recurrence analysis of SCNAs in all studies integrated with gene expression data allowed us to reduce candidate gene lists for 1q, 2p, 6p, 7q and 13q to a limited gene set. Besides the well-established driver genes RB1 (13q-loss) and MYCN (2p-gain) we identified CRB1 and NEK7 (1q-gain), SOX4 (6p-gain) and NUP205 (7q-gain) as novel retinoblastoma driver candidates. Depending on the sample subset and algorithms used, alternative candidates were identified including MIR181 (1q-gain) and DEK (6p gain). Remarkably, our study showed that copy number gains rarely exceeded change of one copy, even in pure tumor samples with 100% homozygosity at the RB1 locus (N = 34), which is indicative for intra-tumor heterogeneity. In addition, profound between-tumor variability was observed that was associated with age at diagnosis and differentiation grades.InterpretationSince focal alterations at commonly altered chromosome regions were rare except for 2p24.3 (MYCN), further functional validation of the oncogenic potential of the described candidate genes is now required. For further investigations, our study provides a refined and revised set of candidate retinoblastoma driver genes.     

Characterization of Staphylococcus species by SDS–PAGE of Whole-Cell and Extracellular Proteins

In this study, a total of fifteen staphylococcal strains belonging to different species were characterized by whole-cell and extracellular protein profiles using sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE). The results are presented as dendrograms after quantitative analysis of the band patterns with a computer program. Visual inspection of protein bands and cluster analysis of protein patterns of to be used 15 strains, representing 10 Staphylococcus species, showed that whole-cell and extracellular protein profiles differed in several protein bands in Staphylococcus aureus, S. epidermidis, S. simulans, and other species of Staphylococcus; however, the differences were insufficient for reliable differentiation of Staphylococcus species by the SDS–PAGE method.     

Neuron Specific Rab4 Effector GRASP-1 Coordinates Membrane Specialization and Maturation of Recycling Endosomes

The endosomal pathway in neuronal dendrites is essential for membrane receptor trafficking and proper synaptic function and plasticity. However, the molecular mechanisms that organize specific endocytic trafficking routes are poorly understood. Here, we identify GRIP-associated protein-1 (GRASP-1) as a neuron-specific effector of Rab4 and key component of the molecular machinery that coordinates recycling endosome maturation in dendrites. We show that GRASP-1 is necessary for AMPA receptor recycling, maintenance of spine morphology, and synaptic plasticity. At the molecular level, GRASP-1 segregates Rab4 from EEA1/Neep21/Rab5-positive early endosomal membranes and coordinates the coupling to Rab11-labelled recycling endosomes by interacting with the endosomal SNARE syntaxin 13. We propose that GRASP-1 connects early and late recycling endosomal compartments by forming a molecular bridge between Rab-specific membrane domains and the endosomal SNARE machinery. The data uncover a new mechanism to achieve specificity and directionality in neuronal membrane receptor trafficking.     

Analysis of the variability of the control region and cytochrome b gene of mtDNA of Capreolus pygargus Pall

Analysis the of cytochrome b gene (1140 b.p.) polymorphism and polymorphism of 79 specimens of the control region (934 b.p.) of mtDNA of the Siberian roe deer Capreolus pygargus from 23 regions of Russia and Kazakhstan has been carried out. The combined alignment of two fragments of mitochondrial DNA revealed 36 haplotypes, which are distributed in three haplogroups. The net distance was 0.8, 1.3, and 1.3%. The specific pattern of haplogroups was described for roe deer of each region (Ural, trans-Ural, Eastern Siberia, Far East, Northeastern China). Unrelated haplogroups were found in populations of the Urals and Siberia. The variation pattern and spatial distribution of mitochondrial lines allowed us to suggest that a haplogroup that initially belongs to C. p. tianschanicus occurs secondarily in C. p. pygargus.     

Serum IGF-I and IGFBP-3 levels of Turkish children during childhood and adolescence: establishment of reference ranges with emphasis on puberty

AIMS/METHODS: We established age- and sex-related reference ranges for serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) levels in 807 healthy Turkish children (428 boys, 379 girls), and constructed a model for calculation of standard deviation scores of IGF-I and IGFBP-3 according to age, sex and pubertal stage. RESULTS: Serum IGF-I and IGFBP-3 concentrations tended to be higher in girls compared to boys of the same ages, but the differences were statistically significant only in pubertal ages (9-14 years) for IGF-I and only in prepubertal ages for IGFBP-3 (6-8 years) (p < 0.05). Peak IGF-I concentrations were observed earlier in girls than boys (14 vs. 15 years, Tanner stage IV vs. V) starting to decline thereafter. IGFBP-3 levels peaked at age 13 and at Tanner stage IV in both sexes with a subsequent fall. Serum levels of IGF-I and IGFBP-3 increased steadily with age in the prepubertal stage followed by a rapid increase in IGF-I in the early pubertal stages. A relatively steeper increase in IGF-I but not in IGFBP-3 levels was observed at age 10-11 years in girls and at 12-13 years in boys which preceded the reported age of pubertal growth spurt. At late pubertal stages, both IGF-I and IGFBP-3 either did not change or decreased by increasing age. Interrelationships between growth factors and anthropometric measurements have been described, and the physiologic consequences of these have been discussed in detail. CONCLUSIONS: Differences in the pattern of IGF-I and IGFBP-3 in the present paper and those reported in other studies emphasize the importance of locally established reference ranges. Establishment of this reference data and a standard deviation score prediction model based on age, sex and puberty will enhance the diagnostic power and utility of IGF-I and IGFBP-3 in evaluating growth disorders in our population.     

Periodontitis in established rheumatoid arthritis patients: a cross-sectional clinical,microbiological and serological study

Introduction

The association between rheumatoid arthritis (RA) and periodontitis is suggested to be linked to the periodontal pathogen Porphyromonas gingivalis. Colonization of P. gingivalis in the oral cavity of RA patients has been scarcely considered. To further explore whether the association between periodontitis and RA is dependent on P. gingivalis, we compared host immune responses in RA patients with and without periodontitis in relation to presence of cultivable P. gingivalis in subgingival plaque.

Methods

In 95 RA patients, the periodontal condition was examined using the Dutch Periodontal Screening Index for treatment needs. Subgingival plaque samples were tested for presence of P. gingivalis by anaerobic culture technique. IgA, IgG and IgM antibody titers to P. gingivalis were measured by ELISA. Serum and subgingival plaque measures were compared to a matched control group of non-RA subjects.

Results

A higher prevalence of severe periodontitis was observed in RA patients in comparison to matched non-RA controls (27% versus 12%, p < 0.001). RA patients with severe periodontitis had higher DAS28 scores than RA patients with no or moderate periodontitis (p < 0.001), while no differences were seen in IgM-RF or ACPA reactivity. Furthermore, RA patients with severe periodontitis had higher IgG- and IgM-anti P. gingivalis titers than non-RA controls with severe periodontitis (p < 0.01 resp. p < 0.05), although subgingival occurrence of P. gingivalis was not different.

Conclusions

Severity of periodontitis is related to severity of RA. RA patients with severe periodontitis have a more robust antibody response against P. gingivalis than non-RA controls, but not all RA patients have cultivable P. gingivalis.     

Retroperitoneal masses mimicking adrenal tumors

ObjectiveTo report 10 cases of neoplasms that were initially thought to be primarily adrenal-derived masses but were later confirmed as tumors of a different origin.MethodsBetween 2000 and 2011, a total of 229 patients underwent adrenalectomy at our institution. Of this overall group, 10 patients had retroperitoneal pathologic conditions mimicking adrenal tumors. Using an institutional review board-approved database, we reviewed the clinical, biochemical, and radiologic characteristics of these 10 patients.ResultsThe study cohort consisted of 4 male and 6 female patients. The mean age of these 10 patients was 48 years. The pathologic conditions included schwannoma (n = 3), leiomyosarcoma (n = 2), and 1 each of metastatic angiosarcoma, metastatic granulosa cell tumor, retroperitoneal hematoma, perivascular epithelioid cell tumor, and bronchogenic cyst. The patient with angiosarcoma had elevated plasma and urine catecholamines and a positive metaiodobenzylguanidine scan, whereas the others had normal findings on biochemical work-up. A percutaneous biopsy was performed preoperatively in 2 patients.All patients, except the patient with hematoma, underwent abdominal exploration, which was laparoscopic in 5, open in 2, and robotic in 2. With exclusion of the patients with angiosarcoma and hematoma, resection was possible in all the remaining patients.ConclusionIn this report we describe our experience with retroperitoneal masses mimicking adrenal tumors. Increased awareness of these unusual pathologic conditions is important for appropriate clinical management of these tumors. The presentation of the patients and the surgical management of these individual pathologic entities are highlighted. (Endocr Pract. 2012;18:335-341)